Promoter-proximal pausing enables transcriptional buffering of RNA polymerase II availability.

In HEK293 cells, modest RNAPII depletion via dTAG triggers widespread transcriptional initiation, pausing, elongation, splicing, readthrough, and impaired cell-cycle progression, with promoter-proximal pausing buffering RNAPII loss.

• Why it matters: RNAPII abundance is essential, but how its cellular levels shape gene regulation was unclear, including whether pausing can protect transcription when RNAPII fluctuates.
• What they did: The study titrated RNAPII levels in HEK293 using the dTAG degradation tag and measured changes across initiation, promoter-proximal pausing, elongation, splicing, termination/readthrough, and cell-cycle progression.
• The result: Genes with strong promoter-proximal pausing were largely resistant to reduced RNAPII, and mRNA output was stabilized under severe depletion by increased transcript half-lives, linking pausing to buffering of RNAPII availability.

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